The low protein diet affects the nonspecific inflammatory response of middle-aged and old mice through mTOR.

OBJECTIVE: To explore the effect of low protein diet on nonspecific inflammatory changes in mice during aging and related mechanisms.

MATERIALS AND METHODS: Thirty-two 14-month-old female KM mice were randomly divided into 4 groups: control group, low protein group, high protein group, high protein + rapamycin group. Hematoxylin-eosin (HE) staining was performed to observe the pathological changes of the liver. Immunohistochemistry of liver sections was performed to detect the expression of CD68 protein. HE staining of colon sections was performed to observe intestinal lymphocyte infiltration. The percentage of spleen CD4+ T and CD8+ T cells was detected by flow cytometry. The mTOR expression in the liver was detected by Western blot and immunohistochemistry.

RESULTS: Compared with the control group, HE staining of liver tissue sections in high-protein group showed the cytoplasm of hepatocytes was loose and disordered, and the hepatic sinus was significantly expanded. Immunohistochemistry of the liver showed a significant increase in CD68 protein expression. Colorectal HE staining showed extensive lymphocyte infiltration. The number of CD4+ T and CD8+ T cells in spleen flow cytometry was significantly decreased (*p < 0.05). Western blot and immunohistochemistry detected a significant increase in mTOR expression in the liver (*p < 0.05, *p < 0.05). In the High Protein+Rapamycin group and Low-protein group, the time-dependent changes were reduced, the numbers of CD4+ T cell and CD8+ T cell in the spleen were significantly increased (*p < 0.05) and the expression of mTOR was significantly reduced (*p < 0.05).

CONCLUSIONS: Low-protein diet is beneficial for delaying the non-specific inflammatory changes of liver and intestines in middle-aged and aged mice, and this effect may be achieved through down-regulation of mTOR.